Although the study of aging is really the study of growth and development, maturity, and senescence, in this grant we plan to focus on mature and senescent rhesus monkeys. Information on the metabolism of muscle from senescent man is understandably scarce. Our group proposes to compare the histological, histochemical, and biochemical data (especially the metabolism of cyclic nucleotides) in skeletal muscle from adult (6 to 12 years) rhesus monkeys (nonhuman primates). We have available at the Oregon Regional Primate Research Center, at least 10 healthy, aged rhesus monkeys. We plan to measure the in situ levels of cAMP and cGMP in muscle from these 2 groups, and to investigate the activity and kinetics (Km and Vmax) of the enzymes involved in the synthesis (adenylate and guanylate cyclases) and degradation (phosphodiesterases) of these compounds (whole homogenates and subcellular fractions). The sensitivity of these enzymes to effector molecules is especially important since the values for maximum enzyme capacity seldom mirror their estimated activity in vivo. Frequently the enzyme capabilities of a given cell are used only minimally and their activity is largely controlled by the intracellular milieu. If time permits, we will study the total activity and the relative amounts of type I and II cAMP-dependent protein kinases. Both types should be studied concomitantly because the total pool and the activation pattern of each type change independently. We are also interested in cGMP-dependent protein kinases, although it is probable that we will not have time for this experiment in the proposed 3-year period. When we discover an enzyme with a change in specific activity, we will study it in depth to determine whether or not it is an "altered" enzyme. Such parameters as heat liability and the amount of activity precipitated by a fixed amount of its antiserum will be compared in mature and aged muscle.